The goal of this A2 revised Phase I STTR is to combine the expertise of an academic team with the resources of Novelos Therapeutics Inc. to study a new injectable small molecule derivative of a proprietary and stabilized formulation of oxidized glutathione (GSSG) called NOV-002. Existing clinical results from trials completed in Russia suggest therapeutic activity of the drug in cancer patients and US clinical trials are in the planning stages. To gain FDA approval of a new drug, preclinical data are required and the approaches proposed in this application are the sole means to advance this agenda. The aims of this STTR are designed to facilitate preclinical pharmacokinetic studies and identify possible pharmacodynamic endpoints of NOV-002 treatment. The plans include identification of drug-induced glutathionylated proteins that may serve as plausible plasma markers and target proteins in bone marrow cells that may be relevant to drug efficacy and mechanism of action. Identification of these proteins will be achieved using antibodies specific for S-glutathionylated residues and immunoblot techniques, proteomic work-up and mass spectrometry. As a further interrogation of the myeloproliferative activity of NOV-002, bone marrow cells from drug treated mice will be used to study the signaling pathways that may be upstream of cytokine and growth factor expression. Such studies should aid in understanding how agents that influence redox balance impact on parameters of hematological proliferation. These aims, in concert with company driven clinical trials, should provide the impetus to enhance the momentum towards eventual drug registration. [unreadable] [unreadable] [unreadable]